1. Field of the Invention
The invention is directed to a process for the preparation of 4-hydroxyisophorone through the oxidation of beta-isophorone.
2. Discussion of the Background
3,5,5-Trimethyl-4-hydroxy-2-cyclohexen-1-one (4-hydroxyisophorone) is described in the literature as a fragrance for tobacco products (JP-OS 81 35 990; CH-PS 549 961; DE-OS 22 02 066), as a flavor and fragrance in foods (CH-PS 549 956; M. Ishihara et al., J. Org. Chem. 1986, 51, 491-5), and as a base material for the synthesis of various pharmaceuticals (N. S. Zarghami et al., Phytochemistry 1971, 10, 2755-61; J. N. Marx and F. Sondheimer, Tetrahedron, Suppl. No. 8, Pt 1, 1-7, 1966). It is generally synthesized by the oxidation of beta-isophorone (3,5,5-trimethyl-3-cyclohexen-1-one) by various methods. ##STR1##
However, a severe limitation existed until recently because no practical procedure was known for preparing beta-isophorone and no further synthetic possibilities were studied. In accordance with DE-OS 37 35 211, however, beta-isophorone can now be prepared conveniently from alpha-isophorone (3,5,5-trimethyl-2-cyclohexen-1-one) by catalytic isomerization, so that at least this problem has been eliminated.
Oxidation in the para-position relative to the carbonyl group in these compounds produces a reactive substituent that permits further syntheses to obtain odorants and flavors identical to natural products, and to prepare Vitamin A derivatives. For this reason, the least expensive and chemically most economical method for carrying out this oxidation step was sought. It must be considered here that beta-isophorone rearranges (back-isomerizes) readily to alpha-isophorone, which does not undergo the desired reaction and is thus unavailable for producing 4-hydroxyisophorone. A need exists, therefore, for a method to keep back-isomerization within limits in addition to the other requirements mentioned.
It is well known that beta-isophorone can be oxidized by air using noble metal catalysts (FR-A 2 335 486). In addition to 4-ketoisophorone and alpha-isophorone, the desired 4-hydroxyisophorone is obtained in this reaction as a byproduct also. 4-Hydroxyisophorone can also be obtained directly from alpha-isophorone in small yields using a biochemical method with Aspergillus niger (JP-OS 81 35 990; Y. Mikami et al., Agric. Biol. Chem. 1981, 45, 791-3). A. Heymes and P. Teisseire obtained 4-hydroxyisophorone in 34% yield by oxidation with monoperphthalic acid (Recherches 1971, 18, 104-8), while N. S. Zarghami and D. E. Heinz (Phytochemistry 1971, 10, 2755-61) disclosed no yield information for the reaction with peracetic acid. J. N. Marx and F. Sondheimer report a yield of 87% from the treatment of beta-isophorone with m-chloroperbenzoic acid, but the recalculation of the results they reported shows only a yield of 56%, which is also in agreement with other information in the literature (Tetrahedron, Suppl. No. 8, Pt. 1, 1-7, 1966; see also O. Isler et al., Helv. Chim. Acta 39, 2041, 1956).
All of the methods published so far have serious deficiencies. On the one hand, the yields are poor, the chemicals used are costly, and it is difficult and expensive to isolate the end product; on the other hand, the processes have large amounts of waste. A technical process based on the available literature can thus be rather surely excluded.